Bladed Ion Slicer

ABSTRACT

Provided herein is a bladed ion slicer for blocking ions in an ion beam that have significant distance from the beam axis. In certain embodiments, the bladed ion slicer comprises a body; a first elongated blade; and a second elongated blade; wherein the ion slicer comprises a slit that extends through the body through which ions pass and wherein the edges of the first and second elongated blades define the entrance of the slit and are pointing towards the ion beam. A mass spectrometer system and method for removing unwanted ions are also provided.

CROSS-REFERENCING

This patent application claims the benefit of U.S. provisional application Ser. No. 61/447,621, filed on Feb. 28, 2011, which provisional application is incorporated by reference herein.

BACKGROUND

Mass spectrometers are used to determine the chemical composition of substances and structures of molecules. Mass spectrometers may comprise an ion source to produce ions—e.g., to ionized neutral molecules—as well as a mass analyzer and ion detector. The mass analyzer may be a time-of-flight (TOF) mass analyzer, for example. TOF mass analyzers may be used to record the mass spectra of compounds or mixtures of compounds by measuring the times for molecular and/or fragment ions of those compounds to travel certain distances.

In orthogonal time of flight mass spectrometry instruments, it is sometimes necessary to control the energy of the beam approaching the orthogonal acceleration region. In such cases, the axial energy of the beam may be controlled to ensure the ions hit the detector after they travel through the free flight region, and to achieve a good resolution. While the vertical position of the ions in the pulser of a time of flight spectrometer can be compensated for using space focusing techniques, the vertical energy leads to turn-around-time issues which cause bad resolution. So typically, in order to achieve high resolution, the ion beam is “sliced” to eliminate ions with excessive “vertical” velocity, i.e., velocity in the same direction as they are pulsed in the time of flight spectrometer, both up and down. This is done by passing an ion beam through a slit in a plate so that the ions which are traveling up or down hit the plate and lose their charge.

BRIEF DESCRIPTION OF THE FIGURES

The accompanying drawings, which are incorporated herein, form part of the specification. Together with this written description, the drawings further serve to explain the principles of, and to enable a person skilled in the relevant art(s), to make and use the claimed systems and methods.

FIG. 1 schematically illustrates a prior art ion slicer.

FIG. 2 schematically illustrates one example of a bladed slicer.

FIG. 3 schematically illustrates another example of a bladed slicer.

FIG. 4 shows perspective views of an exemplary bladed slicer.

FIG. 5 illustrates an exemplary mass spectrometry system in which a bladed slicer may be used.

FIG. 6 shows a possible configuration for a bladed slicer, showing where contamination may occur.

DETAILED DESCRIPTION

Provided herein is a bladed ion slicer for blocking ions in an ion beam that have significant distance from the beam axis. In certain embodiments, the bladed ion slicer comprises a body; a first elongated blade connected to the body; and a second elongated blade connected to the body; wherein the bladed ion slicer comprises a slit that extends through the body through which ions pass and wherein the edges of the first and second elongated blades define the entrance of the slit and are pointing towards the ion beam.

Also provided is a mass spectrometer system comprising: an ion source for producing a ions; a ion guide for guiding the ions; a subject bladed ion slicer; and; an orthogonal time of flight mass analyzer for analyzing the ions, wherein the bladed ion slicer blocks ions that have significant distance from the ion beam from passing from the ion guide to the orthogonal time of flight mass analyzer.

Finally, a method of removing unwanted ions that have significant distance from an ion beam axis is also provided. In certain embodiments, this method comprises: directing a beam of ions at a bladed ion slicer, comprising: a) a body comprising a slit through which ions pass: b) a first elongated blade; and c) a second elongated blade; wherein the edges of the first and second blades are pointed towards the ion beam and define the entrance of the elongated slit, wherein the unwanted ions collide with the blades and are prevented from passing through the slit.

Prior to its entry into an orthogonal time of flight spectrometer, an ion beam is often “sliced” so that ions in the beam that are “vertically” distanced from the beam axis (i.e., distanced in the same direction as pulsing in the downstream flight tube) are blocked. The resultant ion beam (which in certain instances can be referred to herein as a “ribbon” of ions because the top and the bottom parts of the beam have been removed), enters the time of flight spectrometer, and ions are pulsed in an orthogonal direction (i.e., upwards relative to the plane of the ribbon) down the flight tube of the TOF spectrometer. Slicing removes ions that have significant energy in the direction of the pulsing. This result in an increase in the resolution of the mass spectrometer. FIG. 1 schematically illustrates a cross-section of a prior art ion slicer. The prior art ion slicer shown in FIG. 1 shows an ion guide 2, an ion beam 4 that is diverging from the beam axis, and a plate 6 that contains a slit 8. The plate 6 blocks ions that are vertically distanced from the beam axis from passing through slit 8.

A cross-section of one example of a bladed slicer is schematically illustrated in FIG. 2. In general terms, bladed slicer 9 comprises: a) a body 10; b) a first elongated blade 12; and c) a second elongated blade 14; wherein the bladed ion slicer comprises a slit 14 that extends through the body 10 and through which ions pass. As illustrated, the edges (i.e., the sharp, cutting edge) of the first and second elongated blades 16 and 18, respectively define the entrance 20 of the slit and are pointing towards the ion beam (i.e., the edges points in a direction that is counterflow to the ion beam). In particular embodiments and as illustrated in FIG. 2, the edges of the first and second elongated blades are parallel to each another. In other embodiments, the spacing between the edges of the first and second elongated blades may vary and in certain cases may increase or decrease, gradually or in a step-wise manner, from one end of the slit to the other. By shifting the blades from side to side, different slit sizes can be presented to the ion beam to increase sensitivity or resolution. Similarly, shifting the blades sideways could be used to present a fresh surface to the ion beam to decrease charging. In some cases, as illustrated in FIG. 1, the slit has an ion entrance end and an ion exit end, and the ion exit end is wider than the ion entrance end. In particular cases, walls of the slit may be at angle of, e.g., 1° to 15° to one another such that the ion exit end is wider than the ion entrance end, which prevents ions from colliding with the wall of the slit. The slit may have a width in the range of 0.1 mm to 10 mm, although a width in the range of 0.5 mm to 2 mm may be used for many purposes. A bladed ion slicer may be made from a conductive material, e.g., stainless steel or an electrically conductive creamic. The bladed slicer, like a conventional slicer, may be electrically connected to provide a voltage potential that, e.g., accelerates or decelerates the ions entering the slicer. In certain embodiments, at least the blades of the slicer may have a thin coating of a material that improves the surface properties of the slicer, e.g., for edge retention and/or corrosion resistance, hardness or stability. Titanium nitride is an example of such a coating, although other coatings can be used. In certain cases such a device may be a monolithic structure that is made using wire electrical discharge machining. The edge of the blade may in certain cases have a radius or chamfer of between 0 mm and 0.1 mm.

In certain embodiments and as illustrated in FIG. 3, a bladed slicer may comprise a third elongated blade 30 and a fourth elongated blade 32, where, as illustrated, the edges of the third and fourth elongated blades are directed towards the ion beam and are parallel to and proximal to the first and second elongated blades, respectively. In certain cases, the edges of the third and fourth blades may be distanced from edges of the first and second blades by a distance in the range of, e.g., 0.05 mm to 1 mm, respectively, although this distance can vary greatly depending on the desired application. In particular embodiments and as illustrated in FIG. 3, the edges of the first and second elongated blades may recessed relative to the third and fourth elongated blades.

In some embodiments, a bladed ion slicer may comprises at least three blades extending along both sides of the elongated slit, wherein the edges of the blades are pointed towards the ion beam the blades are increasingly recessed towards the elongated slit. FIG. 3 illustrates a blading slicer containing four blades on either side of the slit (blades 32, 34, 36 and 38 being above the slit, and blades 30, 40, 42 and 44 being below the slit), wherein the blades are increasingly recessed towards the slit.

The angle of the blade(s) relative to the axis of the ion beam may vary greatly depending on the desired application, as can the relative angle of the sides of each of the individual blades. In a particular embodiment, the side of the blades that is closer to the longitudinal axis of the ion beam (i.e., the side of the blades that is closer to the slit) is angled in the range of 1 to 30 degrees relative to the longitudinal axis of the ion beam. In certain cases the side of the blades that is further from the longitudinal axis of the ion beam (i.e., the side of the blades that is further from the slit) may in certain cases be is angled in the range of 10 to 60 degrees relative to the longitudinal axis.

FIG. 4 is a diagram illustrating an example of a bladed slicer that contains multiple blades, shown from the ion exit side (top) and ion entrance side (bottom). As shown in FIG. 4, slit 14 extends through body 10, and the entrance of the slit on the ion entrance side of the slicer is defined by elongated blades 16 and 18. As can be seen in FIG. 4, the length of the edges is much wider than the width of the beam, thus allowing for the slit to be moved periodically sidewise to expose fresh blade surfaces to the ion beam.

A mass spectrometer system is also provided. In certain embodiments, the system comprises: an ion source for producing ions; an ion guide for guiding the ions; a bladed ion slicer as described above; and a time of flight mass analyzer, e.g., an orthogonal time of flight mass analyzer, for analyzing the ions. As noted above, the bladed ion slicer blocks ions that have significant distance from the ion beam axis from passing from the ion guide to the orthogonal time of flight mass analyzer. The bladed ion slicer may in certain cases be distanced from the ion exit end of the ion guide by a distance in the range of 0.5 cm to 10 cm. In certain cases the distance may be increased or decreased to block more or less ions from entering the spectrometer. In particular cases, the system may contain a further ion slicer immediately downstream of the ion slicer described above so that the sliced ion beam that passes through the upstream bladed ion slicer are further sliced by the downstream ion slicer. In some cases, the downstream slicer may be of the same design of the upstream bladed ion slicer in that it may contain a body comprising a slit through which ions pass, a first elongated blade; and a second elongated blade, wherein the edges of the first and second elongated blades are pointed towards the ion beam and define the entrance of the slit.

The above-described bladed ion slicer can be used in any mass spectrometry system, particularly one in which has an orthogonal time of flight mass spectrometer. Many examples of such systems are known. FIG. 5 illustrates an example of a tandem mass spectrometer 100 (a quadrupole/time-of-flight or ‘q-TOF’) that includes a time-of-flight (TOF) mass analyzer and that incorporates a bladed slicer described above. FIG. 5 shows the positioning of the subject bladed slicer relative to other components in a single exemplary machine. Other configurations of the elements shown in FIG. 5 would be apparent to one of skill in the art.

As shown in FIG. 5, the tandem mass spectrometer 100 includes an ion source 110 and a skimmer 115 at the downstream end of the ion source for filtering the introduction of ions into the vacuum stages of the mass spectrometer. In a first vacuum stage 120, analyte ions are guided through an ion guide 122, such as an octapole, ion lenses 123 and a first mass analyzer 124. Ions that are not eliminated in the first mass analyzer 124 pass into a second vacuum stage 130 via an aperture. The second vacuum stage 130 includes, in sequence, a collision cell 132, in which analyte ions may be fragmented into smaller ions and neutral particles, an ion guide 134 and a further ion guide 136 maintained at a dc voltage.

The product ions output from the collision cell are guided through the ion guide 134 and the ion guide 136 into a subject slicer 135 that is used to block ions having a high degree of transverse displacement (displacement in the direction ions are pulsed into a TOF, as discussed above), before the entrance to an orthogonal acceleration chamber of the TOF mass analyzer 140. The ions blocked by bladed slicer 135 accumulate on its surface.

Ions that pass through bladed slicer 135 enter an ion pulser 142 having a back plate and an acceleration column. To start the ion's flight through the flight tube 143, a high voltage pulse is applied to the back plate that accelerates a pancake of ions through a stack of plate in the acceleration column of ion pulser 142. The ions then travel through the flight tube in a direction toward an electrostatic ion minor 145. The ion minor 145 reverses the flow of ions back in the ‘upstream’ direction of the flight tube. The ions reversed by the ion minor flow toward a detector 148, which registers the impact of ions and their flight times through the flight tube 143.

In particular embodiments, the bladed slicer may be movable such that once a portion of the blades of the slicer have been sufficient contaminated by ion collisions, the slicer may be moved laterally so that the ion beam is directed to an uncontaminated part of the slicer. This may be done by, e.g., venting the chamber containing the slicer, and moving the slicer to the side so that the an uncontaminated part of the blade is lined up with the ion beam.

A method of removing unwanted ions that have significant distance from the ion beam axis is also provided. In general terms, this method comprises directing a beam of ions at a bladed ion slicer, comprising: a body comprising a slit through which ions pass, a first elongated blade; and c) a second elongated blade; where the edges of the first and second blades are pointed towards the ion beam and define the entrance of the elongated slit and wherein the unwanted ions collide with the blades and are prevented from passing through the slit. In particular cases, the ion may slicer contain three or more elongated blades on each side of the slit, wherein the edges of the elongated blades are directed towards the ion beam and the elongated blades are increasingly recessed towards the slit. The beam of ions may have exited an ion guide that is upstream of the bladed slicer. In particular cases, the width of the slit, or the distance between the exit of the ion guide and the entrance of the bladed slicer may be increased or decreased to allow more or less ions through the slit.

As the requirements for resolution and abundance in mass spectrometry have increased, the flux of ions entering the slicer has increased, the velocity of the beam has been reduced, and the vertical dimension of the slits has been reduced. The consequence is an increased susceptibility to voltage asymmetries in the vertical axis. These voltage asymmetries can cause a field which deflects the ions up or down, depending on polarity. If the ions are deflected by the first slit, the result is a loss in abundance. If the ions are deflected by the last slit, the result is a loss of resolution and abundance both. The losses are observable if a high flux of ions is introduction into the slicer for an extended period of time. The abundance loss can exceed 90% over time. One mechanism to minimize the abundance and resolution loss is through the defocusing of the ion beam due to the changing electric potential on both top and bottom slit. This problem, may in theory result from an accumulation of neutral non-conductive molecules and undissipated charge on the surface of the slit. The problem is particularly pronounced when running high concentration protein and peptide samples. While different surface chemistries can help a little to avoid the charge build up, a geometrical solution has proven to offer significant advantages in both the ion current that can be tolerated and the time before degradation of the signal begins. Instead of using a flat plate with a slit cut in it, the surface which the ions impact is sloped sharply away from the slit opening. This reduces the deflection of ions approaching the slit because the field created by the charging is partially shielded, the resistance layer on the surface builds more slowly and is thinner, and the ion density striking the surface is reduced. Conventionally, the slope of the impact surface is 90 degrees to the beam. With the slope at, e.g., 20 degrees, the neutral build up is distributed across 3 times the area, so the insulation in ohms of the surface is decreased by a factor of 3 for any given molecular beam deposition. Likewise, the ion density striking the contaminated surface is reduced by sin(20), again a factor of three. So the resulting voltage on the surface is reduced by about a factor of about 9. In some cases, a sharp edge with a small radius typically in the range of 20+−20 microns may be specified, which can be made using wire EDM method.

The blade should pointed toward the incoming the ion beam. To avoid contaminating this horizontal surface with ion impacts, it may be tapered away from the beam. The angle is around 5 degrees for this taper because that is a little more than the beam divergence. This value should be set as low as possible, yet still greater than the ion beam divergence which will vary depending on the instrument design. The shallower the angle of the impact surface, the more the charging effect should be suppressed. The impact slope angle of about 20 degrees on the energy filtering slits, i.e. the middle slit and the exit slit may be used. This means the metal itself may have an angle of about 15 degrees. In order to achieve such a narrow wedge shape the impact slope may be machined conventionally, and then the internal 5 degree surface is removed using wire EDM. This is a low force metal removal technique which keeps the sharp edge intact. It is also a very precise machining technique which helps to accurately create the 3 dimensional shape. In one embodiment, the base material is stainless steel. The surface is then coated with titanium nitride. This hard conductive surface is easier to clean and experimentally shows a small additional decrease in contamination rate. In addition to the 5 degree internal angle and the 20 degree charging slope, a shield can be added in front of the middle slit. The shield is made slightly larger than the beam so that ions won't hit it, but its proximity further decreases the charging effect, by 20 to 40% based on the electric field modeling. The front slits also have a sloped impact region, but since the top and bottom slits are spaced 3 mm apart relatively few ions hit them and a voltage on the surface deflects the beam less. Since they are independently tunable, beam deflection can be compensated for to a certain extent. The can be made with a larger radius on the front of the blade, or even a chamfer or a flat spot 0.1 to 0.5 mm. This makes them easier to produce and less fragile. The skimmer-slicer design with a mid slit and an exit slit with 5 degree internal angle and 20 degree charging surface angle has decreased the charging by about a factor of 10. This means that users can either run about 10 times the sample load without losing abundance or they can run about 10 times as long before suffering abundance losses.

Multiple blade slicing is also proposed. As shown in FIG. 6, each blade can protects the subsequent blade from excessive ion impact. In some embodiments (and as illustrated in FIG. 6), the “back” surface of each blade is not exposed to the beam, so no charging can occur there. As a result, the electric potential created by this surface provides partial shielding of the ion beam from the field perturbation created by the charging on the subsequent blade. With 3 or 4 blades the result is a factor of 2 or 3× reduction in the perturbation of the fields, and hence an expected 2× to 3× increase in the length of time before the instrument performance is degraded.

The geometric modifications to the slicer design significantly improve the longevity of the operation. However, after a very long operation involving analysis of high loadings of analytes (such as, for example, microgram injections of protein digest), even the best slicer designs may begin to show abundance and/or resolution losses. The only thing one can do is vent the instrument, disassemble the optics, clean the slits with an elaborate and time consuming chemical process, reassembly the optics, pump down the instrument, wait a day or two to re-establish the pressure, and then retune the instrument.

To solve this issue it is proposed to use a continuous horizontal slit that could be shifted horizontally by a distance corresponding to the diameter of the beam. The contaminated surface can be moved so that it is no longer in the ion beam path, and a new fresh surface is exposed. For example, if the beam diameter is about 4 mm, an indexing part with discrete steps of 4 mm is created The available space is the practical limit for the number of horizontal slit positions, but one can have up to 10 positions or more.

By using a semi-infinite horizontal slit, the horizontal position is of little importance to either ion transmission or resolution, other than the necessity of moving over the beam width to find a fresh uncontaminated surface.

In operation, when the abundance or resolution degradation is observed and slit charging is suspected, indexing one position can be taken as a corrective action. As a result, instead of a significant overhaul after a certain period of time running high concentration samples, the customer can index the slit position several times and postpone the downtime for months. Indexing of the slit position can be performed very rapidly so that the inside of the vacuum manifold is open for a short period of time. As a result, the instrument can be pumped back and be operational within 1-2 hours. In one embodiment, an automated indexing will allow avoiding venting the instrument altogether. The desired position of the slit can be selected through the software user interface. Stepper motor mounted on the slicer body provides the motion of the slit. In another embodiment, different openings can be realized along the horizontal dimension of the indexable slit. This way the transmission/resolution of the instrument can be adjusted mechanically without the need of venting and part replacement.

The foregoing description of the invention has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed. Other modifications and variations may be possible in light of the above teachings. The embodiments were chosen and described in order to best explain the principles of the invention and its practical application, and to thereby enable others skilled in the art to best utilize the invention in various embodiments and various modifications as are suited to the particular use contemplated. It is intended that the appended claims be construed to include other alternative embodiments of the invention; including equivalent structures, components, methods, and means.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination. All combinations of the embodiments are specifically embraced by the present invention and are disclosed herein just as if each and every combination was individually and explicitly disclosed, to the extent that such combinations embrace operable processes and/or devices/systems/kits.

As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of events recited or in any other order which is logically possible. 

1. An ion slicer for blocking ions in an ion beam that have significant distance from the beam axis, comprising: a) a body; b) a first elongated blade connected to the body; and c) a second elongated blade connected to the body; wherein the ion slicer comprises a slit that extends through said body through which ions pass and wherein the edges of said first and second elongated blades define the entrance of said slit and are pointing towards said ion beam.
 2. The ion slicer of claim 1, wherein the edges of said first and second elongated blades are parallel to each another.
 3. The ion slicer of claim 1, further comprising a third elongated blade and a fourth elongated blade, wherein the edges of said third and fourth elongated blades are directed towards said ion beam and are parallel to and proximal to said first and second elongated blades, respectively.
 4. The ion slicer of claim 3, wherein the edges of said first and second elongated blades are recessed relative to said third and fourth elongated blades.
 5. The ion slicer of claim 3, wherein said ion slicer comprises at least three blades extending along either side of said elongated slit, wherein the edges of said blades are pointed towards said ion beam.
 6. The ion slicer of claim 1, wherein the side of said blades that is further from the longitudinal axis of the ion beam is angled in the range of 10 to 60 degrees relative to the longitudinal axis of the ion beam.
 7. The ion slicer of claim 6, wherein the side of said blades that is closer to the longitudinal axis of the ion beam is angled in the range of 1 to 30 degrees relative to said longitudinal axis.
 8. The ion slicer of claim 1, wherein the slit has an ion entrance end and an ion exit end, and the walls that extend from said ion entrance end and sais ion exit end are at an angle in the range of 1° to 15° relative to one another such that said ion exit end of said slit is larger than the ion entrance end of said slit.
 9. The ion slicer of claim 1, wherein said slit has a width in the range of 0.1 mm to 10 mm.
 10. The ion slicer of claim 1, wherein said ion slicer is a monolithic structure made using wire EDM.
 11. The ion slicer of claim 1, wherein said ion slicer is made from a conductive ceramic.
 12. The ion slicer of claim 1, where the edge of the blade has a radius or chamfer of between 0 mm and 0.1 mm.
 13. A mass spectrometer system comprising: a) an ion source for producing a ions; b) a ion guide for guiding said ions; c) an ion slicer of claim 1; and; d) an orthogonal time of flight mass analyzer for analyzing said ions, wherein said ion slicer blocks ions that have significant distance from the ion beam axis component from passing from said ion guide to said orthogonal time of flight mass analyzer.
 14. The mass spectrometer system of claim 13, wherein said ion slicer is distanced from the ion exit end of said ion guide by a distance in the range of 0.5 cm to 10 cm.
 15. The mass spectrometer system of claim 13, further comprising a second ion slicer downstream of the ion slicer of c).
 16. The mass spectrometer system of claim 13, wherein said second ion slicer comprises: a) a body comprising a slit through which ions pass; b) a first elongated blade; and c) a second elongated blade; wherein the edges of said first and second elongated blades are pointed towards said ion beam and define the entrance of said slit.
 17. A method of removing unwanted ions that have significant distance from the ion beam axis and/or high transverse velocity component, comprising: directing a beam of ions at an ion slicer, comprising: a) a body comprising a slit through which ions pass: b) a first elongated blade; and c) a second elongated blade; wherein the edges of said first and second blades are pointed towards said ion beam and define the entrance of said elongated slit, wherein said unwanted ions collide with said blades and are prevented from passing through said slit.
 18. The method of claim 17, wherein said ion slicer comprises three or more elongated blades on each side of said slit, wherein the edges of said elongated blades are directed towards said ion beam and said elongated blades are increasingly recessed towards said slit.
 19. The method of claim 17, wherein said beam of ions have exited an ion guide that is upstream of said ion slicer.
 20. The method of claim 17, comprising adjusting the width of said slit to allow more or less ions through said slit. 